tbuckley/cabot-search huggingface dataset:
Start so young? Defense of the primary HPV test as a screening test for cervical cancer in women aged 25 and over in Brazil.
Authors: Jose Iran Costa, Jurema Telles O. Lima, Mozart J. T. Sales, Leticia Katz
Journal: Journal of Clinical Oncology (2023)

e17531 Background: Cervical cancer (CC) is the most frequent type of cancer on woman at reproductive age and on the puerperal pregnancy cycle in Brazil. It is a disease that can be prevented with the resources already available at Brazil’s public healthcare system.The most important risk factor for developing cervical cancer is infection with human papillomavirus (HPV). With the covid 19 pandemic, there was an advance in the possibility of carrying out an HPV test by PCR by through the government initiative "uterus is life" and we was asked what age should start the HPV test in the proposed screening organized. Methods: Descriptive, observational, cross sectional study Carried two cancer centers( using an adapted form, between 2020 2021 Sociodemographic data, cancer characteristics. Descriptive statistics were used to analyze the data and evaluation of secondary data from the ministry of health (DATASUS) This study was approved by the institution’s ethics committee. Recife, Brazil. Results: From 2021 -2022, 240 patients with CC mean age 50,48y (SD ± 13.8; range 24-87), 15, 8 % &lt; 35 y, age of first sexual intercourse: mean age 16,7 (SD ± 3.2, range 11- 30) and 79,6 % &lt; 18y. age of first pregnancy mean 18 (SD ± 6.54; range 12- 36) 77,4 % &lt; 18 y.In the year 2019 of the number of patients undergoing treatment in the Brazilian public system (SUS), by age group, 14.076 patients &lt;35 y (58%). $821,000 was spent in 2019 on anticancer chemotherapy for CC in women &lt; 35 y. Conclusions: With a view to establishing an organized screening policy using the HPV test, considering the window of opportunity to diagnose the non-invasive cervical cancer stage, the onset of sexual activity and the age of first pregnancy among patients with invasive cervical cancer and the representativeness of patients with &lt; 35 years undergoing treatment for advanced CC. The "Utero é Vida" initiative recommended starting the screening of the HPV test from the age of 25 y, in addition to intensifying vaccination coverage against HPV.
Molecular testing utilization in patients with advanced non-small cell lung cancer (NSCLC) in Washington (WA) state.
Authors: Lauren Shih, Qin Sun, Catherine R. Fedorenko, Kaiyue Yu, Li Li, Karma L. Kreizenbeck, Veena Shankaran, Scott David Ramsey
Journal: Journal of Clinical Oncology (2023)

6596 Background: Therapies targeted at driver mutations (e.g. EGFR, ALK) in NSCLC have contributed to improved patient survival. While current guidelines recommend that all patients diagnosed with stage IV NSCLC undergo molecular testing to determine eligibility for targeted therapies, real-world testing patterns have not been well described. In a retrospective study using cancer registry and insurance claims, we evaluated rates of molecular testing in a population-based sample of NSCLC patients in WA. Methods: We linked WA state cancer registry records from 2017-2019 with claims records for Medicare, Medicaid, and two large commercial insurers. Patients diagnosed with stage IV NSCLC who had continuous insurance enrollment for 2 months prior to and 12 months following diagnosis were identified. Using insurance claims data, we identified patients who received any molecular testing (either testing for specific markers or comprehensive molecular profiling). We compared proportions of patients who received and did not receive molecular testing by insurance type, race, ethnicity, gender, and diagnosis (Dx) year. We performed a multivariate regression analysis to determine factors associated with completion of molecular testing. Results: 1048 eligible patients were identified. The median age was 70. Patients were predominately insured by Medicare (62.6%) and non-Hispanic white. 90.3% of all patients underwent molecular testing. Molecular testing rates were similar between white and non-white patients (90.4% vs 89.2%, p=0.647). Testing rates were significantly lower among Hispanic patients vs non-Hispanic patients (77.8% vs 90.7%, p=0.018). Testing rates were lowest among Medicaid enrollees (86.4%) compared to Medicare (88.4%), commercial (97.2%) or multiple insurances (94.9%) (p=0.0018). A multivariate analysis demonstrated that patients age ≥65 and Medicaid patients were less likely to receive molecular testing while females were more likely to receive testing; year of Dx did not impact testing rates (Table). Conclusions: While the rate of adherence to recommended molecular testing was high in the overall cohort, testing rates were lower in Hispanic patients, older patients, males, and those with Medicaid insurance. Given the therapeutic implications of testing, drivers of these observed disparities warrant further study to ensure equitable access to efficacious treatment. [Table: see text]
Phase 2 study of HDAC inhibitor tucidinostat in combination with anti-PD-1 antibody in patients with locally advanced or metastatic urothelial carcinoma.
Authors: Zhuowei Liu, Lijuan Jiang, Xiangdong Li, Yunlin Ye, Zhiming Wu, Xin An, Yanxia Shi, Kai Yao
Journal: Journal of Clinical Oncology (2023)

e16563 Background: Tucidinostat (also known as chidamide), a novel histone deacetylase (HDAC) inhibitor, has been approved for treatment of patients (pts) with relapsed or refractory peripheral T-cell lymphoma and advanced hormone receptor-positive breast cancer in China. Tislelizumab (a PD-1 checkpoint inhibitor) is currently approved for pts with PD-L1-high locally advanced or metastatic urothelial carcinoma (UC) who progressed during/following platinum-containing therapy in China. However, the response rate of tislelizumab as monotherapy is limited in UC. The aim of this study was to evaluate the efficacy and safety of tucidinostat combined with tislelizumab in pts with locally advanced or metastatic UC. Methods: This study is an open-label, single-center, phase Ⅱ trial. Patients who previously failed systemic platinum-based chemotherapy with UC were included, regardless of PD-L1 status. Eligible pts received 30 mg oral tucidinostat twice weekly (BIW) in combination with 200 mg tislelizumab by intravenous drip every three weeks (Q3W). This is a Simon's two-stage design. All pts were treated until progression or unacceptable toxicity in two years. The primary endpoint was objective response rate (ORR). The secondary endpoints included progression free survival (PFS), disease control rate (DCR), overall survival (OS), the safety and tolerability. Results: From Jan. 2021 to Sep. 2022, 26 pts were enrolled (median age 62 y, range 31-74y), of whom 24 were evaluable for response per RECIST 1.1 criteria. One pt was lost to follow-up and one withdrew the group due to sudden cerebral infarction. Complete response (CR) was observed in 2 pts, while partial response (PR) was observed in 8 pts, with an ORR of 41.7% (10/24). The DCR was 62.5%. The median PFS was 4.6 months. Most adverse events (AEs) were grade 1 or 2. The most common grade 3 AEs were neutropenia 11.5%, thrombocytopenia 11.5%, leukopenia 7.7%, anemia 7.7%, anorexia 7.7%, creatinine increased 3.8%. One pt experienced grade 4 immuno-pneumonia was permanently discontinued. One pt was on maintenance therapy of tucidinostat without immunotherapy because of interstitial pneumonia. Conclusions: The preliminary data indicate that tucidinostat combined with tislelizumab might be a potentially effective regimen with a manageable safety profile in UC. The study remains ongoing and updated results will be presented later. Clinical trial information: NCT04562311 .
Final results of a phase II trial of prolgolimab with platinum-based therapy and bevacizumab in patients with advanced cervical cancer.
Authors: Sergey Fogt, Timur Andabekov, Yana Shamsutdinova, Mikhail Dvorkin, Elena Artamonova, Valerii Chistyakov, Ruslan Zukov, Vladimir Moiseenko, Marina Nechaeva, Svetlana Odintsova, Natalia Fadeeva, Nikolai Kislov, Denis Tantsyrev, Sergei Tjulandin, Eugeniy Fomin, Iuliia Linkova, Arina Zinkina-Orikhan, Mariia Shustova, Lyudmila Zhukova
Journal: Journal of Clinical Oncology (2023)

5536 Background: Here we present the final results of single-arm phase II CAESURA (NCT03912402) study of prolgolimab (anti-PD-1 antibody) with platinum doublet and bevacizumab in subjects with advanced cervical cancer (CC). Methods: 58 patients (pts) with metastatic or recurrent/persistent CC with measurable disease received prolgolimab (3 mg/kg) Q3W together with paclitaxel, platinum drug (cis- or carboplatin) and bevacizumab for 6 cycles and then therapy with prolgolimab and bevacizumab until disease progression or toxicity. Objective response rate (ORR) was assessed by central radiology review per RECIST 1.1 (primary endpoint) and iRECIST criteria. CT scans were performed after 9 and 18 weeks of treatment and in case of suspicion on disease progression. Results: Distant metastases at screening had 42 pts, 16 had recurrent or persistent CC. The median age of pts was 48 [38; 58] years old. Squamous cell carcinoma was diagnosed in 50 of 58 subjects. PD-L1 CPS ≥ 1 (22C3) was found in 45 pts, CPS &lt; 1 in 6 cases. ORR per RECIST 1.1 was 63.8% (37 of 58 pts) and included 2 complete, 35 partial responses. ORR per iRECIST was 70.7% (41 of 58 pts) with 2 complete and 39 partial responses. At the cut-off date (12 months) PFS (secondary endpoint) per RECIST 1.1 criteria counted 8.5 (95% CI 5.7; 10.9) months, per iRECIST criteria it reached 13.1 (95% CI 8.1; 13.6) months. Median overall survival was not reached. Any grade adverse events (AEs) occurred in 98% (57/58) of pts, of them in 69% (40/58) they were related to study treatment, including 12 cases of severe events (gr. 3 or higher). Immune-related AEs (irAEs) occurred in 38% (22/58) of pts. The most common irAEs were gr. 1–2 endocrine disorders (26%), including thyroid disorders and one case of gr. 2 adrenal insufficiency. Other important irAEs included 2 cases of enterocolitis (gr. 3 and 4), 1 case of dermatitis (gr. 3), several cases of gr. 2–3 transaminase elevation (9%). In 15 pts at least one component of study treatment was discontinued due to AE, of them 4 events were related to study treatment (including immune-related enterocolitis and adrenal insufficiency). Conclusions: Prolgolimab in combination with chemotherapy and bevacizumab demonstrated promising efficacy, known and acceptable safety profile in pts with advanced CC. Phase III placebo-controlled trial evaluating prolgolimab with chemotherapy and bevacizumab (NCT03912415) as first-line therapy option in subjects with CC is ongoing. Clinical trial information: NCT03912402 .
Use of poly (adp-ribose) polymerase inhibitors (PARPi) in metastatic castration resistant prostate cancer (mCRPC) patients stratified by homologous recombination repair mutations.
Authors: Roby Antony Thomas, Anupama Vasudevan, Simon Blanc, Rushir J. Choksi, Sandy English, Lindsay Aton, Marni Brisson Tierno, Mike Gart
Journal: Journal of Clinical Oncology (2023)

e17053 Background: Approval of the PARPi in May 2020 caused a paradigm shift in the treatment of mCRPC patients with homologous recombination repair (HRR) mutations. Gaps remain in the optimal prescribing of PARPi in eligible patients, with negative consequences on clinical outcomes. The goal of this study was to look at PARPi prescribing practices in patients with HRR mutations overall and by sub-mutation. Methods: The Integra Connect PQ-deidentified real-world database was used, comprising over 1 million cancer patients across 275 sites of care, of which 80% were community practices and 20% academic settings. We performed medical chart reviews and identified 261 patients with HRRm mCRPC that received therapy between 5/1/2020 to 1/24/2023. We segmented patients into BRCA-positive with or without other HRR mutations, ATM positive without BRCA mutations and with or without other HRR mutations, and other HRR mutations without BRCA or ATM mutations. We compared utilization of PARPi in HRRm patients by sub-group. Descriptive statistics were used to assess proportions of utilization of PARPi treatment among HRRm patients. Proportions were compared using the two-proportion z-test. Results: Among HRRm mCRPC patients with prior next-generation hormonal agent (NHA) treatment, the use of PARPi is 61% (158 of 261). Among HRRm mCRPC patients who received PARPi after prior NHA treatment, 76% (78 of 103) were in the BRCA positive group, 62% (48 of 78) in the ATM positive group and 40% (32 of 80) in the other HRR mutations positive group. Patients in the BRCA positive group were more likely to receive a PARPi than those in either the ATM or other HRR mutations group (p &lt; 0.01). Patients harboring ATM mutations were more likely to receive a PARPi than patients with non-BRCA HRR mutations (p &lt; 0.01). Conclusions: This real-world study shows an opportunity to increase rates of PARPi treatment in patients with HRRm mCRPC across all HRR gene mutations. mCRPC patients with BRCA and ATM mutations were more likely to receive PARPi than those with other HRR mutations.
Use of machine learning derived features from CT and H&amp;E whole-slide images to predict overall survival in head and neck squamous cell carcinoma.
Authors: Bolin Song, Amaury Leroy, Kailin Yang, Vidya Sankar Viswanathan, Xiao Li, Jonathan Lee, Sarah Stock, Pingfu Fu, Nabil F. Saba, Shlomo A. Koyfman, James S. Lewis, Eric Deutsch, Anant Madabhushi
Journal: Journal of Clinical Oncology (2023)

6086 Background: Computed tomography (CT) and H&amp;E whole-slide images (WSI) have been found to carry rich prognostic information for patients diagnosed with head and neck squamous cell carcinoma (HNSCC). However, most machine learning models aimed for outcome prediction only took advantage of single image modality. In this work, we developed and validated a prognostic machine learning method incorporating both CT and WSI to predict overall survival in HNSCC patients. Methods: Matched radiographic CT scans and digitized WSI were acquired from the Cleveland Clinic for 167 HNSCC patients, including 120 HPV-associated oropharyngeal cancer and 47 laryngeal cancer. Both primary tumor and the largest suspicious lymph node were annotated on CT scans and primary tumor was delineated on H&amp;E WSI. We split the dataset into training and validation set using a 7:3 ratio, which resulted in 119 patients in the training set and 48 for hold-out validation. We applied a machine learning model (M_ML) using both CT and WSI as input to perform end-to-end predictions of overall survival. We used the harrell’s concordance index (C-index) to evaluate the prognostic performance. Finally, we performed the multivariable cox proportional hazard analysis adjusting for clinicopathological variables (i.e. age, gender, smoking pack-year [PY], AJCC 7 th edition overall stage, and treatment modality) to validate the independent prognostic significance of the model. Results: The combined machine learning model M_ML (C-index = 0.81) outperformed the model using CT images alone (C-index = 0.63) and WSI alone (C-index = 0.64) on the validation set. In multivariable analysis, M_ML is still statistically significant accounting for clinicopathologic factors (p = 0.0007). Conclusions: This pilot study shows that a multi-omic machine learning model utilizing both radiographic CT and digitized WSI can predict HNSCC overall survival and outperforms models using only a single modality. [Table: see text]
CRI-CCTG-0003/IND.240: An immunotherapy platform study in platinum-resistant high grade serous ovarian cancer (IPROC).
Authors: Helen Mackay, Anna Tinker, Brad Nelson, Dmitriy Zamarin, Kunle Odunsi, Stephanie Lheureux, Susan Ellard, Alannah Smrke, Pierre-Olivier Gaudreau, Tess Faulkner, Ana Rosa Saez-Ibanez, Dongsheng Tu, Janet Ellen Dancey
Journal: Journal of Clinical Oncology (2023)

TPS5617 Background: Identifying new treatments for patients with platinum-resistant high grade serous ovarian cancer (HGSC) is a priority. Although several biological features of HGSC suggest inherent immunogenicity, immunotherapy has had limited efficacy to date. IPROC is an adaptive platform trial designed to evaluate multiple immunotherapy combinations selected and informed by an expert panel. IPROC accommodates both biomarker-agnostic and biomarker-directed combinations. Protocol and sub study specific translational studies are conducted on archived diagnostic tissue and serial prospective blood and tumor sample collection. Methods: IPROC is an open-label, multi center, phase II platform trial. Eligibility includes HGSC histology; progression within 6 months of the last platinum regimen; &lt;1 prior line of chemotherapy for platinum resistant disease (unlimited prior lines for platinum sensitive); prior treatment with immunotherapy allowed (provided not discontinued for toxicity), ECOG 0/1. Patients must be willing and able to undergo study procedures. The primary endpoint is ORR (RECIST1.1). Secondary endpoints include iRECIST ORR, RECIST/iRECIST progression free and overall survival and safety. Exploratory objectives include whole exome sequencing and immune profiling of tumor and blood samples to identify biomarkers and new immunotherapy strategies/combinations for future evaluation. Tumor biopsy occurs at baseline, cycle 2 and progression (voluntary) with blood and plasma collected at each cycle and on progression. All sub studies use Simon 2-stage design with 10 patients (pts) enrolled in each stage. At the end of stage 1, in the absence of response, a modified cohort based on biomarker selection may be created through protocol amendment. In each substudy a null hypothesis that the objective response rate (ORR) is ≤5% is tested against a one-sided alternative that the ORR is ≥ 25%. A combination would be accepted as active if ≥4/20 pts respond with α=0.02 and power of 0.76. As of January 19, 2023, 2 sub studies are open and 12 patients have accrued. Sub study A is evaluating the combination of durvalumab and BA3011, a conditionally active anti-AXL humanized monoclonal antibody (IgG1) conjugated to monomethyl auristatin E (MMAE) in AXL overexpressing HGSC. Sub study B is evaluating durvalumab plus BA3021, a CAB anti-receptor tyrosine kinase orphan receptor 2 (ROR2) humanized monoclonal antibody (IgG1) conjugated to MMAE in ROR2 overexpressing HGSC. Further sub studies are planned (NCT04918186). Clinical trial information: NCT04918186 .
Socioeconomic and demographic barriers associated with delays in pancreatic cancer germline genetic testing.
Authors: Xianghui Zou, Baho Sidiqi, Brooke Tortorella, Sunita Patruni, Leora Rezak, Catherine M. Alfano, Christopher Hollweg, Noah D. Kauff, Daniel King
Journal: Journal of Clinical Oncology (2023)

e18506 Background: Germline genetic testing is recommended for patients with pancreatic ductal adenocarcinoma (PDAC). We identified associations between patient social profiles and delays in obtaining germline genetic testing from New York’s largest healthcare system. Methods: Patients with PDAC were identified using our EMR between Mar 2016 and Feb 2022 with an IRB-approved protocol. Median income was extrapolated using zip code. Social vulnerability index (SVI) was obtained from CDC ATSDR website. Date of diagnosis (DOD) was recorded as the date of biopsy. Delays of testing were calculated as the difference between DOD and the date of germline test. Social work needs, sources of income, and insurances were captured by EMR review of social work notes. Pearson correlation, Mann-Whitney, and Chi-square tests were used for statistical analysis. Results: We identified 104 (34%) patients with germline tests. Other than ethnicity, there was no demographic difference between patients who performed tests and patients who did not (Table). Pearson analysis between income and delays showed a negative correlation (r=-0.3033, p=0.0018). Patients who received social security and were unemployed/disabled had significant delays in testing (167d) compared to patients receiving social security and retired (30d, p=0.0318) or patients receiving salaries (13d, p=0.0002). African Americans and Hispanics, classified as underserved minority, had significant delays (92d) in testing compared to those not underserved (21d, p=0.0018). In addition, African Americans had significant delays (92d) compared to White patients (13d, p=0.0002). Patients with social work needs (12 total: 6 home care, 3 transportation, 2 financial assistance) had significant delays in testing (109d) compared to those without needs (24.5d, p=0.0028). Patients from zip codes with SVI&gt;0.5 had non-significant delays (40.5d) compared to patients from zip codes with SVI&lt;0.5 (26d, p=0.1817). In addition, patients with Medicare had significant delays (40d) compared to those with Medicare and supplementary insurances (15d, p=0.0205). Conclusions: PDAC patients with delays in germline testing were more likely African American and Hispanic, had lower income with social work needs, received social security, or lacked supplemental insurance. Interprofessional collaborations may be required to prompt germline tests. [Table: see text]
Outcomes and safety of subsequent treatments after immune- and anti-VEGF therapy in patients with metastatic clear-cell renal cell carcinoma: Outcomes from a tertiary referral hospital.
Authors: Jose Carlos Tapia, Charlotte Toms, Yishen Wang, Agne Jovaisaite, Matthew Nicholas Young, Francesca Jackson-Spence, Thomas Powles, Bernadett Szabados
Journal: Journal of Clinical Oncology (2023)

e16533 Background: Immune checkpoint inhibitors (ICIs) and anti-VEGFs, either in combination or sequentially, are the standard of care in first- and second-line (2L) setting for metastatic clear-cell renal cell carcinoma (mRCC); however, there is uncertainty about the subsequent lines. We describe real-world outcomes and safety of using anti-VEGFs such as cabozantinib (CABO), axitinib (AXI), and sunitinib (SUN) after ICIs and anti-VEGF therapies in patients (pts) with mRCC. Methods: A retrospective audit was performed on pts with mRCC treated between June 2014 and June 2022 at the St Bartholomew’s Hospital, London, UK. Baseline patient and treatment characteristics, best response, dose modifications and survival outcomes were collected. Kaplan-Meier methods were used to evaluate the progression-free survival (PFS) and overall survival (OS). Results: Overall, 188 pts with mRCC were treated. We analysed 69 pts of whom 45 (65%), 16 (23%) and 8 (12%) pts received CABO, AXI, and SUN, respectively, as subsequent treatment after prior ICIs and anti-VEG. Baseline characteristics are described. Median follow-up was 36 months (95% CI: 31.6 - 55.3). Overall, the partial response (PR) and stable disease (SD) rates were 9% and 45%, respectively. Eleven percent, 12% and 0% pts achieved PR and 53%, 25% and 31% achieved SD on CABO, SUN and AXI, respectively. In general, the median PFS was 9.9 months (95% CI: 6.5-14.2) and the median OS was 16.5 months (95% CI: 11.6-23.5). One-year PFS and 1-year OS was 36% and 51%, respectively. PFS and OS by treatment are reported. The number of pts who experienced toxicities that required dose reductions was higher with CABO (58%) and SUN (37%) than with AXI (6%). The median time to dose reduction was 2.4, 1.4, and 1.4 months for CABO, SUN and AXI. Conclusions: In our centre, CABO was the most common subsequent treatment after previous ICIs and anti-VEGF. Taking into account the retrospective and single-centre nature of the collected data these results support the activity of CABO, AXI and SUN in this setting. AXI was well tolerated with less dose modifications. [Table: see text]